ABSTRACT
Objective: To investigate the high expression of MUC15 in promoting proliferation, migration and invasion in osteosarcoma (OS) cell and its potential mechanism. Methods: The expressions of MUC15 in OS patients were analyzed from GEO Datasets, tumor cell lines and clinical samples. The roles of MUC15 in OS were explored by CCK-8, flow cytometry, transwell and western blot assay, respectively. Results: MUC15 was highly expressed in osteosarcoma, and there was a significant negative correlation between MUC15 and the prognosis. Knockdown of MUC15 in HOS and U-2OS could promote tumor cell apoptosis, down-regulate the expression of MMP2/9, reduce the epithelial interstitial transition and silence the Wnt/b-Catenin signal pathway. Conclusion: The high-expression of MUC15 promotes the proliferation, migration and invasion of osteosarcoma through anti-apoptosis, increasing the invasive ability by epithelial interstitial transition, and activating the Wnt/b-Catenin signal pathway.
ABSTRACT
STUDY DESIGN: A three-level rat tail caudal intervertebral disc (IVD) degeneration (IVDD) model was established to study effects of static compression on extracellular matrix (ECM) remodeling and integrin signaling in IVDs during IVDD. OBJECTIVE: The aim of this study was to investigate the effect of compression force on ECM remodeling and integrin signaling in IVDs during IVDD. SUMMARY OF BACKGROUND DATA: Integrins sense mechanical environment alteration via binding to ECM ligands and trigger intracellular signaling for pathological ECM remodeling during IVDD. However, the role of compression force in ECM remodeling and integrin signaling during IVDD remains elusive. METHODS: Compared with the classical one-level rat tail IVDD model that exerts axial stress on the 8th to 9th caudal vertebral bodies, a three-level model was established by using an Ilizarov-type apparatus to exert stress on the 7th to 10th caudal vertebral bodies in rat tails for four weeks. To exclude side effects from surgical stab injury on manipulated discs, intact coccygeal (Co) disc Co8-9 was analyzed. RESULTS: In three-level IVDD model, significant degeneration of the Co8-9 disc was observed. Quantitative real-time polymerase chain reaction (qRT-PCR) showed elevated mRNA expression of collagen types I, III, and V; matrix metalloproteinases (MMPs) 2, 3, 9, 13, 14; and decreased mRNA expression of collagen type II in Co8-9 disc. Compression loading altered the expression of integrin α2ß1 (upregulated) and α10ß1 (downregulated) in NP cells, and activated integrin downstream signaling. By contrast, one-level model showed more severe disc degeneration and ECM remodeling. Integrin α1, α2, α11, and ß1 were upregulated, whereas α10 was downregulated. Similar activation of integrin signaling was observed. CONCLUSION: Static compression altered collagen and MMP expression, and promoted ß1 integrin expression and signaling in IVD. Compared with one-level rat tail IVDD model, three-level model showed milder effects on disc degeneration, ECM remodeling, and integrin expression, suggesting one-level model might involve other causes that induce IVDD via mechanisms independent of compression force. LEVEL OF EVIDENCE: N/A.
